The goals of this project are to study physiological and pathological factors which may influence brain metabolism and the kinetics of metabolite transport at the blood-capillary endothelial cell interface (blood-brain barrier), and relate the findings to the corresponding conditions in vivo. Brain energy metabolism, glycolysis, amino acid flux and metabolite transport are to be studied during and after ischemia or 30 minute periods of perfusion with blood having pO2's of less than 10 mmHg, 20mmHg and 30mmHg. Cerebral oxygen delivery, tissue oxygenation capillary recruitment and regional blood flow will be followed during and after perfusion with blood having a left shifted hemoglobin saturation curve (P50 approximately 15 mmHg). With the use of a compartmental model, cerebral glucose concentration and distribution space are to be investigated in brains following perfusion with blood having one of several low arterial oxygen tensions. The contribution of blood pH to transport kinetics of various metabolites will be studied during and after exposure to blood having a pH in a non-physiologic range in order to identify the functional groups on the carrier and determine if blood (H ion) influences the velocity of the reaction under physiological conditions of pH.